Antidepressant effect of bright light therapy on patients with Alzheimer's disease and their caregivers.

Background: As a non-pharmacologic treatment, bright light therapy (BLT) is often used to improve affective disorders and memory function. In this study, we aimed to determine the effect of BLT on depression and electrophysiological features of the brain in patients with Alzheimer's disease (AD) and their caregivers using a light-emitting diode device of 14000 lux. Methods: A 4-week case-control trial was conducted. Neuropsychiatric and electroencephalogram (EEG) examination were evaluated at baseline and after 4 weeks. EEG power in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) bands was calculated for our main analysis. Demographic and clinical variables were analyzed using Student's t test and the chi-square test. Pearson's correlation was used to determine the correlation between electrophysiological features, blood biochemical indicators, and cognitive assessment scale scores. Results: In this study, 22 in-patients with AD and 23 caregivers were recruited. After BLT, the Hamilton depression scale score decreased in the fourth week. Compared with the age-matched controls of their caregivers, a higher spectral power at the lower delta and theta frequencies was observed in the AD group. After BLT, the EEG power of the delta and theta frequencies in the AD group decreased. No change was observed in blood amyloid concentrations before and after BLT. Conclusion: In conclusion, a 4-week course of BLT significantly suppressed depression in patients with AD and their caregivers. Moreover, changes in EEG power were also significant in both groups.

Functional near-infrared spectroscopy in elderly patients with four types of dementia.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is commonly used to study human brain function by measuring the hemodynamic signals originating from cortical activation and provides a new noninvasive detection method for identifying dementia. AIM: To investigate the fNIRS imaging technique and its clinical application in differential diagnosis of subtype dementias including frontotemporal lobe dementia, Lewy body dementia, Parkinson's disease dementia (PDD) and Alzheimer's disease (AD). METHODS: Four patients with different types of dementia were examined with fNIRS during two tasks and a resting state. We adopted the verbal fluency task, working memory task and resting state task. Each patient was compared on the same task. We conducted and analyzed the fNIRS data using a general linear model and Pearson's correlation analysis. RESULTS: Compared with other types of dementias, fNIRS showed the left frontotemporal and prefrontal lobes to be poorly activated during the verbal fluency task in frontotemporal dementia. In Lewy body dementia, severe asymmetry of prefrontal lobes appeared during both verbal fluency and working memory tasks, and the patient had low functional connectivity during a resting state. In PDD, the patient's prefrontal cortex showed lower excitability than the temporal lobe during the verbal fluency task, while the prefrontal cortex showed higher excitability during the working memory task. The patient with AD showed poor prefrontal and temporal activation during the working memory task, and more activation of frontopolar instead of the dorsolateral prefrontal cortex. CONCLUSION: Different hemodynamic characteristics of four types of dementia (as seen by fNIRS imaging) provides evidence that fNIRS can serve as a potential tool for the diagnosis between dementia subtypes.

Targeting neuroinflammation in Alzheimer's disease: from mechanisms to clinical applications.

Alzheimer's disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer's disease research; however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer's disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer's disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer's disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer's disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer's disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer's disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed.

Effect of light therapy on delirium in older patients with Alzheimer's disease-related dementia.

Light therapy has been used as a non-pharmacologic treatment to modulate biorhythms in patients with mental and psychological conditions. These conditions include affective disorders and depression. Delirium is a syndrome characterized by an acute change in a patient's mental status. We hypothesized that light therapy might suppress delirium in patients with Alzheimer's disease (AD). A 4-week randomized controlled trial was conducted in which AD participants were randomly assigned to a treatment group or a control group. Delirium, defined by the Confusion Assessment Method (CAM), was evaluated at baseline and after 4 weeks. The Neuropsychiatric Inventory (NPI) and Zarit Caregiver Burden Interview (ZBI) were also conducted to assess the behavior of patients and the burden of their caregivers. For this study, 61 participants were initially recruited. A total of 34 and 27 participants were included in the treatment and control groups, respectively. After treatment with light therapy, the CAM score decreased during the second and fourth week. The NPI score in the therapy group also decreased during the second and fourth week. From the caregiver's perspective, after light therapy, the ZBI score significantly decreased during the second and fourth week. Compared with the control group, patients who underwent CAM and NPI assessments showed a small but significant improvement after 4 weeks of light therapy. In conclusion, a course of 4-week light therapy significantly suppressed delirium in patients with AD. The combined effects of light therapy and conventional treatment were superior to that of conventional treatment alone.

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer's disease.

BACKGROUND: Retinal biomarkers of Alzheimer's disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD. OBJECTIVE: Our study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs). METHODS: Non-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters. RESULTS: Seventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 µm), FRTs of the four quadrants (290.35 ± 13.05 µm of inferior quadrant, 294.68 ± 9.37 µm of superior quadrant, 302.97 ± 6.52 µm of nasal quadrant, 286.02 ± 13.74 µm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892. CONCLUSION: Our study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology. Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx.

Retinal Levels of Amyloid Beta Correlate with Cerebral Levels of Amyloid Beta in Young APPswe/PS1dE9 Transgenic Mice before Onset of Alzheimer's Disease.

OBJECTIVES: Retina abnormalities are related to cognitive disorders in patients with Alzheimer's disease (AD). Retinal amyloid beta (Aß) can be labeled by curcumin. We measured Aß content in the cerebrum and retina of APPswe/PS1dE9 (APP) transgenic mice with early age to investigate the correlation between cerebrum and retina. METHODS: APP mice and age-matched wild-type mice were investigated every month from age 2 months to 6 months to assess changes in Aß content in the retina and cerebrum. At the beginning of each month, mice were fed a curcumin diet (50 mg/kg/day) for 7 consecutive days. The Aß levels in the retina and cerebrum were measured by ELISAs. Correlations were identified between retinal and cerebral Aß contents using Pearson's correlation. RESULTS: In the absence of curcumin, there was a significant correlation between Aß contents in the retina and cerebrum of APP mice (r = 0.7291, P = 0.0014). With increasing age, Aß-mediated degenerative change in the cerebrum (P < 0.001 in 5 months) and retina (P < 0.01 in 5 months) increased significantly. The inhibitory effect of curcumin on the Aß level was significant in the cerebrum (P < 0.001) and retina (P < 0.01) of older APP mice in the early stage of life. CONCLUSION: We observed a significant correlation between the Aß content in the retina and Aß content in the cerebrum of APP mice. Our data suggest an appropriate time to measure retinal Aß. Although curcumin can label Aß in the retina, it also suppresses Aß levels and weakens the degree of correlation between Aß in cerebrum and retina tissues.